Preparation of 4-cyano-4&#39;-hydroxybiphenyl

ABSTRACT

The invention relates to a preparation process for 4-cyano-4&#39;-hydroxybiphenyl, said process comprising the protection of the hydroxy group of 4-phenyl-phenol, acylation of the protected 4-phenyl-phenol group, conversion of the resulting ketone into an acid, amidification of the acid thus obtained, dehydration of the resulting amide and deprotection of the hydroxy group.

This application is a 371 of PCT application FR98/00290 filed Feb. 16,1998.

The invention relates to a preparation process for4-cyano-4'-hydroxybiphenyl. This compound is known as an intermediateand used, for example, in the synthesis of monomers of liquid crystalpolymers (GB 2002767) (J. Polym. Sci., Part C: Polymer Letters, Vol. 28,345-355 (1990); J. Mater, Chem., 1993, 3(6), 633-642) or for theformation of specific polysiloxanes (U.S. Pat. No. 5,262,052).

4-cyano-4'-hydroxy-biphenyl can be prepared as described in theApplication EP 44759 or in J. Mater. Chem., 1933, 3(6), 633-642, byreacting 4-bromo-4'-hydroxy-biphenyl with copper cyanide. Anotherpreparation method described in the application U.S. Pat. No. 5,262,052,consists of reacting di(4-methoxyphenyl)zinc with 4-bromobenzonitrile inthe presence of Ni(PPh₃)₄. The disadvantage of these processes is thatthey use toxic agents such as copper cyanide. A subject of the inventionis a preparation process which does not use a toxic agent such as coppercyanide or which uses less toxic agents than those described in thestate of the art.

The invention thus relates to a preparation process for4-cyano-4'-hydroxybiphenyl, the process comprising:

protection of the hydroxy group of 4-phenyl-phenol,

acylation of the protected 4-phenyl-phenol group,

conversion of the resulting ketone into an acid,

amidification of the acid thus obtained,

dehydration of the resulting amide, and

deprotection of the hydroxy group.

The hydroxy group can be protected by the standard methods which arewell known to a person skilled in the art. The hydroxy group of4-phenyl-phenol can be protected, for example, by alkylation. The alkylgroup can be a linear or branched alkyl group having up to 5 carbonatoms, examples are methyl, ethyl, propyl, isopropyl, butyl and t-butylgroups.

All the acylation methods which are well known to a person skilled inthe art can be used. For example, a Friedel-Crafts acylation can beused.

The reactions in which the ketone is converted into an acid, the acidinto an amide and the amide into a cyano group by dehydration, can beimplemented by using standard methods known to a person skilled in theart. As regards the amidification, the preferred method consists ofconverting the acid function into a halide which is then treated withammonia or an amine.

The deprotection method used depends on the reagent used for thedeprotection reaction.

The following examples are presented to illustrate the above proceduresand must in no case be considered as a limit to the scope of theinvention.

EXAMPLE 1

Preparation of 4-methoxybiphenyl

A solution of 102 g (0.6 mol) of 4-phenylphenol in a mixture of 800 mlof ethanol and 200 ml water is prepared at 40° C., 48 g (1.2 mol) ofsoda is added, a solution is obtained into which 126 g (1 mol) ofdimethyl sulphate is poured over 35 minutes. The reaction medium istaken to reflux for 9 hours. A mixture of 400 ml of water and 400 ml ofethanol is added while warm, and the reaction medium is cooled down to20° C., separated, washed with water then with ethanol. After drying,101 g (91% yield) of 4-methoxybiphenyl is obtained in the form of awhite powder.

EXAMPLE 2

Preparation of 4-acetyl-4'-methoxy biphenyl

A solution of 87.5 g (0.656 mol) of aluminium chloride in 365 ml of1,2-dichloroethane is prepared at 20° C. The solution is cooled down to0° C. and 33.6 g (0.328 mol) of pure acetic anhydride is added over 15minutes without exceeding 10° C. An orange-coloured solution is obtainedwhich is left under agitation for 50 minutes and which is then pouredover 30 minutes into a solution of 60 g (0.326 mol) of4-methoxy-biphenyl in 610 ml of 1,2-dichloroethane. A deep red solutionis obtained which is taken to reflux for 4 hours. It is cooled down to0° C. and the reaction medium is poured into 300 ml of 3N hydrochloricacid. After decanting, the aqueous phase is re-extracted withdichloromethane (3×100 ml). The combined organic phases are washed withwater (3×100 ml), and the solvents are eliminated under reducedpressure. The residue is taken up in 450 ml of ethanol, followed bycooling down, drying and washing with ice-cooled ethanol (2×100 ml).

After drying, 47.9 g (65% yield) of 4-acetyl-4'-methoxy biphenyl isobtained in the form of a beige powder.

EXAMPLE 3

Preparation of 4'-methoxy-4-biphenylcarboxylic acid

A solution of 64.7 g (1.61 mol) of soda in 560 ml water is prepared at0° C. 69.9 g (0.44 mol) of bromine then 260 ml of 1,4-dioxane are addedsuccessively. A yellow solution is obtained which is cooled down to 0°C. and which is added over 10 minutes, without exceeding 10° C., to asuspension of 28 g (0.12 mol) of 4'-acetyl-4-methoxybiphenyl in amixture of 750 ml of 1,4-dioxane and 510 ml water. The reaction mediumis agitated for 1 hour at approximately 20° C., a solution of 15.5 g ofsodium sulphite in 160 ml water is added and taken to reflux for 10minutes. 76 ml of concentrated hydrochloric acid is added and thereaction medium is left under agitation whilst being cooled down, for 1hour. After drying, washing with water and drying at 50° C., 25.5 g of4'-methoxy-4-biphenyl carboxylic acid is obtained in the form of a whitepowder (yield: 93%).

EXAMPLE 4

Preparation of 4'-methoxy-4-biphenyl carboxamide

18 ml (0.24 mol) of thionyl chloride is added to a solution of 23.4 g(0.1 mol) of 4-methoxy-4-biphenyl carboxylic acid in 200 ml of anhydroustoluene and taken to boiling under reflux for 7 hours. The excessthionyl chloride is eliminated by distillation under reduced pressure.Ammonia is introduced until the reaction is complete. 250 ml water isadded, followed by drying, washing with water and drying. 20.3 g of4'-methoxy-4-biphenyl carboxamide is obtained in the form of whitecrystals (yield: 87%).

EXAMPLE 5

Preparation of 4-cyano-4'-methoxy-biphenyl

A fine suspension of 44.2 g (0.24 mol) of 2,4,6-trichloro-1,3,5-triazinein 190 ml of DMF is added to a suspension of 20 g (0.09 mol) of4'-methoxy-4-biphenyl carboxamide in 370 ml of DMF and is left underagitation for 20 hours. A mixture of 300 ml water and 200 g crushed iceis added to the reaction medium and extraction is carried out withmethylene chloride (3×100 ml). The combined organic extracts are washedwith water (2×200 ml), dried over magnesium sulphate, and the solvent iseliminated by distillation under reduced pressure. The dry extract istaken up in 80 ml ethanol and agitation is carried out for 15 minutes,followed by crystallization by the addition of 200 ml of heptane,cooling down to ambient temperature under agitation, drying and washingwith heptane. After drying, 13.7 g of 4-cyano-4'-methoxy biphenyl isobtained in the form of a beige powder (yield: 72.5%).

EXAMPLE 6

Preparation of 4-cyano-4'-hydroxy-biphenyl

A mixture of 10 g of 4-cyano-4-methoxy biphenyl and 30 g of pyridiniumchloride is taken to 200° C. for 2 hours. 50 ml of pyridine then 50 mlof 1N hydrochloric acid are added at 110° C. Extraction is carried outwith chloroform (100 then 25 ml). The combined organic extracts arewashed twice with 100 ml water, dried over magnesium sulphate, and thesolvent is eliminated by distillation under reduced pressure. 7 g (75%yield) of 4-cyano-4'-hydroxy-biphenyl is obtained in the form of a beigepowder.

What is claimed is:
 1. A process for the preparation of4-cyano-4'-hydroxy-biphenyl comprising protecting the hydroxy of4-phenyl-phenol, subjecting the protected 4-hydroxy-phenyl-phenol toacylation, converting the acylated product into a carboxylic acid,amidifying the carboxylic acid, dehydrating the resulting amide to formthe protected 4-cyano-biphenyl and deprotecting the hydroxy to form4-cyano-4'-hydroxy-biphenyl.
 2. The process of claim 1 wherein thehydroxy of 4-phenyl-phenol is protected by alkylation.
 3. The process ofclaim 1 wherein the acylation is a Friedel-Crafts acylation.
 4. Theprocess of claim 1 wherein the amidification of the acid comprisesforming the acid halide which is then reacted with ammonia.
 5. A processfor the preparation of 4-cyano-4'-hydroxy-biphenyl comprising reacting4-phenyl-phenol to alkylation to form 4-alkoxy-biphenyl where the alkoxyhas 1 to 5 carbon atoms, reacting the latter with an acid anhydride toform 4-acyl-4'-alkoxy-biphenyl, reacting the latter to form4'-alkoxy-4-biphenyl carboxylic acid, reacting the latter with thionylchloride to form 4'-alkoxy-4-biphenyl carboxylic acid chloride, reactingthe latter with ammonia to form 4'-alkoxy-4-biphenylcarboxamide,dehydrating the latter to form 4-cyano-4'-alkoxy-biphenyl andhydrolyzing the latter to form 4-cyano-4'-hydroxy-biphenyl.